The goal of this Senior Scientist Research and Mentorship Award is to foster the careers of junior faculty (Assistant Professors) who have exceptional potential as independent investigators in the field of alcoholic liver injury and fibrosis. The PI has 25 years experience as an NIH funded investigator and has mentored over 50 trainees, many of whom are now leaders in their own right in the field of academic hepatology and liver research. His longstanding record of accomplishment in understanding the pathogenesis of hepatic fibrosis and cancer has helped spawn an exciting new discipline that continues to attract talented junior MD, PhD, and MD/PhD scientists to his laboratory. Studies in his laboratory and those of his mentees in the Division of Liver Diseases of the Mount Sinai School of Medicine have coalesced with the recent award of a NIAAA P20 grant focused on alcoholic liver injury and fibrosis. The synergistic efforts conducted by these young investigators explore the basis of hepatic injury and inflammation by exploiting novel models that include zebrafish, embryonic stem cells, genetic mouse models, and liver cell co-cultures. Their work will advance our understanding of oxidant stress, transcriptional gene regulation, dendritic cell biology and the impact of viral infection on the pathogenesis of alcoholic liver injury and fibrosis. Moreover, the interwoven projects undertaken by the mentees, under the overarching guidance of the PI, will span the full translational spectrum from fundamental cell and molecular biology to analysis of human tissues, and ultimately could translate into novel diagnostics and therapeutics for patients with chronic liver disease due to alcohol. It is anticipated that the mentoring relationships supported by this award will yield a cadre of highly trained young faculty capable of advancing the field of alcohol research, and who will likely emerge among the next generation of leaders in the field. PUBLIC HEALTH RELEVANCE: Alcoholic liver disease remains a highly prevalent and often lethal complication of alcohol abuse, whose etiology is incompletely understood. Understanding the basis of alcoholic liver disease could improve the health of millions of Americans afflicted by this problem. In support of this objective, the PI will commit to mentoring outstanding young scientists who can advance the field and improve outcomes of this disease.